Tau-targeting active immunotherapy slows progression and reduces pathology in mouse models of tauopathy

Abstract

A novel class of active immunotherapy, consisting of proprietary T-helper peptide linked to a B-cell epitope, is being developed to target tau in Alzheimer's disease (AD). These experimental therapies generate antibodies that have demonstrated binding to pathological tau in vitro, and efficacy in cell-based tau aggregation assays comparable to monoclonal antibodies. Here, we report the ability of one such tau-targeting immunotherapy, p5555kb, to prevent the progression of tau pathology using two distinct mouse models. P301L mice were immunized with p5555kb and showed greater survival rates at 210 days than saline-inoculated control mice. The efficacy of p5555kb against tau seeding in vivo was assessed by injecting C57BL6 mice with tau fibrils purified from post-mortem human AD brain tissue. Immunization with p5555kb significantly reduced the amount of tau inclusions detected by immunohistochemistry at 9 months post-injection, as compared to saline inoculation. This study demonstrates that p5555kb is effective at inducing functional tau-targeting antibodies, which prevented the onset of adverse phenotypes associated with tau pathology in vitro and in vivo.

Keywords: Alzheimer's disease; active immunotherapy; tau; tau seeding; tauopathy.